Glypican-3 expression in hepatocellular tumors: diagnostic value for preneoplastic lesions and hepatocellular carcinomas

Wang, Xiaoying; Degos, Françoise; Dubois, Sylvie; Tessiore, S.; Allegretta, Mark; Guttmann, Ronald D.; Jothy, Serge; Belghiti, Jacques; Bédossa, Pierre; Paradis, Valérie

doi:10.1016/j.humpath.2006.05.016

Cited by 207 publications

(167 citation statements)

References 24 publications

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“…Using this ELISA, we measured sGOLPH2 levels in the range of 1.5-60 g/mL with 5% of sera exceeding the upper range. The sGOLPH levels in this study are in the range of serum levels found for interleukin-2 (IL-2), IL-6, IL-8, tumor necrosis factor-␣, 11 CCSA-2 (colon cancer-specific antigen 2), 12 Glypican-3 in patients with HCC, 13 or C-reactive protein (CRP).…”

Section: Golph2 Protein Expression In Hepatocellularmentioning

confidence: 49%

Golgi phosphoprotein 2 (GOLPH2) expression in liver tumors and its value as a serum marker in hepatocellular carcinomas

et al. 2009

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Hepatocellular carcinomas (HCCs) and bile duct carcinomas (BDCs) have a poor prognosis. Therefore, surveillance strategies including sensitive and specific serum markers for early detection are needed. Recently, Golgi Phosphoprotein 2 (GOLPH2) has been proposed as a serum marker for HCC, but GOLPH2 expression data in liver tissues was not available. Using tissue microarrays and immunohistochemistry, we semiquantitatively analyzed GOLPH2 protein expression in patients with HCC (n ‫؍‬ 170), benign liver tumors (n ‫؍‬ 22), BDC (n ‫؍‬ 114) and normal liver tissue (n ‫؍‬ 105). A newly designed sandwich enzyme-linked immunoassay (ELISA) was used to analyze GOLPH2 levels in the sera of patients with HCC (n ‫؍‬ 62), hepatitis C virus (HCV) (n ‫؍‬ 29), BDC (n ‫؍‬ 10), and healthy control persons (n ‫؍‬ 12). By immunohistochemistry 121/170 (71%) of HCC showed strong GOLPH2 expression, which was significantly associated with a higher tumor grade (P ‫؍‬ 0.01). A total of 97/114 (85%) BDCs showed a strong GOLPH2 expression which proved to be an independent prognostic factor for overall survival (P < 0.05). Serum levels of GOLPH2 measured by ELISA were significantly elevated in patients with HCC with underlying HCV infection (median 18 mg/L, P < 0.05) and patients with BDC (median ‫؍‬ 14.5 mg/L, P < 0.01) in comparison to healthy controls (median 4 mg/L). Conclusion: GOLPH2 protein is highly expressed in tissues of HCC and BDC. GOLPH2 protein levels are detectable and quantifiable in sera by ELISA. In patients with hepatitis C, serial ELISA measurements in the course of the disease appear to be a promising complementary serum marker in the surveillance of HCC. GOLPH2 should be further evaluated as a serum tumor marker in BDC on a larger scale.

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Section: Golph2 Protein Expression In Hepatocellularmentioning

confidence: 49%

Golgi phosphoprotein 2 (GOLPH2) expression in liver tumors and its value as a serum marker in hepatocellular carcinomas

et al. 2009

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“…[34][35][36][37][38][39] GPC3 immunoreactivity has a reported sensitivity of 77% and specificity of 96% in the diagnosis of small HCC; therefore, GPC3 positivity is a strong argument for malignancy. 40,41 The staining pattern is usually cytoplasmic but may be membranous or canalicular (Fig. 4).…”

Section: Emerging Tumor Markersmentioning

confidence: 99%

Pathologic diagnosis of early hepatocellular carcinoma: A report of the international consensus group for hepatocellular neoplasia

2008

Hepatology

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“…[18][19][20][21] In the current series, 10 cases of ␤-catenin-activated HCA without HCC were negative for GPC3 staining (data not shown). However, considering that only 64% of HCC developed on normal liver were previously shown to be positively stained by GPC3, 22 we need to identify new markers of malignant transformation of the ␤-catenin-activated adenomas and therefore precisely understand the malignant transformation of this type of HCA. Furthermore, we found that SAA overexpression in inflammatory adenomas included all cases of lesions previously classified as telangiectatic FNH.…”

Section: Discussionmentioning

confidence: 99%

Hepatocellular adenoma subtype classification using molecular markers and immunohistochemistry

et al. 2007

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Hepatocellular adenomas (HCA) with activated ␤-catenin present a high risk of malignant transformation. To permit robust routine diagnosis to allow for HCA subtype classification, we searched new useful markers. We analyzed the expression of candidate genes by quantitative reverse transcription polymerase chain reaction QRT-PCR followed by immunohistochemistry to validate their specificity and sensitivity according to hepatocyte nuclear factor 1 alpha (HNF1␣) and ␤-catenin mutations as well as inflammatory phenotype. Quantitative RT-PCR showed that FABP1 (liver fatty acid binding protein) and UGT2B7 were downregulated in HNF1␣-inactivated HCA (P < 0.0002); GLUL (glutamine synthetase) and GPR49 overexpression were associated with ␤-catenin-activating mutations (P < 0.0005), and SAA2 (serum amyloid A2) and CRP (C-reactive protein) were upregulated in inflammatory HCA (P ‫؍‬ 0.0001). Immunohistochemistry validation confirmed that the absence of liver-fatty acid binding protein (L-FABP) expression rightly indicated HNF1␣ mutation (100% sensitivity and specificity), the combination of glutamine synthetase overexpression and nuclear ␤-catenin staining were excellent predictors of ␤-catenin-activating mutation (85% sensitivity, 100% specificity), and SAA hepatocytic staining was ideal to classify inflammatory HCA (91% sensitivity and specificity). Finally, a series of 93 HCA was unambiguously classified using our 4 validated immunohistochemical markers. Importantly, new associations were revealed for inflammatory HCA defined by SAA staining with frequent hemorrhages (P ‫؍‬ 0.003), telangiectatic phenotype (P < 0.001), high body mass index, and alcohol intake (P < 0.04). Previously described associations were confirmed and in particular the significant association between ␤-catenin-activated HCA and hepatocellular carcinomas (HCC) at diagnosis or during follow-up (P < 10 -5 ). Conclusion: We refined HCA classification and its phenotypic correlations, providing a routine test to classify hepatocellular adenomas using simple and robust immunohistochemistry. (HEPATOLOGY 2007;46:740-748.) H epatocellular adenomas (HCA) are rare benign liver tumors, most frequently occurring in women who are using oral contraception. Although HCA are mostly found as a single nodule, the presence of more than 10 in the liver indicates a specific nosological entity termed liver adenomatosis. 1 Two genetic alterations, the biallelic inactivation of hepatocyte nuclear factor 1 alpha (HNF1␣) and the activating mutation of ␤-catenin, have been described in HCA. 2,3 Recently, a comprehensive analysis of genetic, pathological, and clinical features in a series of 96 HCA enabled the identification of 4 HCA subtypes. 4 Biallelic HNF1␣ mutations defined the first group of HCA, phenotypically characterized by marked steatosis, lack of cytological abnormalities, and inflammatory infiltrates. Presence of a ␤-catenin-activating mutation defined the second group of HCA representing 15% of the cases generally characterized by a higher risk of malignant tr...

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Glypican-3 expression in hepatocellular tumors: diagnostic value for preneoplastic lesions and hepatocellular carcinomas

Cited by 207 publications

References 24 publications

Golgi phosphoprotein 2 (GOLPH2) expression in liver tumors and its value as a serum marker in hepatocellular carcinomas

Golgi phosphoprotein 2 (GOLPH2) expression in liver tumors and its value as a serum marker in hepatocellular carcinomas

Pathologic diagnosis of early hepatocellular carcinoma: A report of the international consensus group for hepatocellular neoplasia

Hepatocellular adenoma subtype classification using molecular markers and immunohistochemistry

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